The atom numbering of the sugar moiety of a nucleic acid monomer shown herein follows atom numbering routinely used on the basis of naturally occurring ribonucleotides (adenosine, cytidine, guanosine, uridine, etc.) (see chemical structural formulas given below). Also, the atom numbering of a naturally occurring nucleobase follows atom numbering routinely used for each of pyrimidine bases (thymine, uracil, and cytosine) and purine bases (adenine, guanine, and hypoxanthine) (see chemical structural formulas given below). The same holds true for substitution products derived therefrom. However, the atom numbering of a heterocyclic ring that is not derived therefrom follows atom numbering generally used.

With rapid progress or development of leading-edge research on biotechnology including genomic drug discovery; genetic diagnosis, genetic therapy; etc, various oligonucleic acids such as DNA and RNA have been increasingly used in treatment, diagnosis, and the like in recent years.
The use of oligonucleic acids in treatment includes the inhibition of the expression of a target gene related to a disease or the inhibition of the functions of a target protein. Promising treatment methods are, for example: an antisense method which involves forming double-stranded DNA/mRNA or RNA/mRNA through Watson-Crick hydrogen bonding from single-stranded DNA or RNA complementary to target mRNA to inhibit the translation process of the mRNA into a target protein; an antigene method which involves forming a triplex using an artificial nucleic acid for double-stranded DNA principally constituting a target gene to suppress the expression of the target gene at the transcription level, a decoy method which involves designing double-stranded DNA having a sequence common to a gene recognized by a transcription factor, which is a protein that recognizes a particular double-stranded DNA sequence on the chromosome and regulates gene expression, and administering this double-stranded DNA into cells, thereby suppressing the transcription through the inhibition of the binding of the transcription factor to the target gene; and nucleic acid aptamers that inhibit the functions of a protein through specific binding to a target protein molecule on the basis of the three-dimensional structure of a nucleic acid; and a ribozyrne method which involves inhibiting the translation of mRNA into a target protein through hydrolysis with nuclease such as RNase or DNase.
The use of oligonucleic acids in diagnosis includes, for example, a method which involves constructing an artificial nucleic acid having a sequence specifically binding to a target gene related to a disease, and using this artificial nucleic acid as a probe to diagnose the disease. Another method employs, as a DNA probe, a molecular beacon that has a stem-loop structure and contains a fluorescent substance and a fluorescence emission-inhibiting substance (quencher) in Its structure so as to emit fluorescence upon binding to target RNA.
RNA interference (RNAi) is basically a phenomenon where a double-stranded RNA of approximately 100 base pairs homologous to a particular region in a target gene to be functionally inhibited is transferred into cells and degraded by the action of dicer in the cytoplasm into double-stranded RNAs of approximately 20 to 25 base pairs, which then form RNA/protein complexes (RISC: RNA-induced silencing complex) with a plurality of proteins so that this complex binds to the homologous site of mRNA produced from the target gene to strongly suppress the expression of the target gene (Non Patent Literature 1). Recently, it has been revealed that use of an artificially synthesized short double-stranded RNA of 20 to 24 bases (small interfering RNA: siRNA) also causes a similar phenomenon. A method suppressing the expression of a target gene by use of such siRNA has received attention not only as a useful research approach but as application to pharmaceutical use. This RNAi method is reportedly effective for suppressing gene expression at a very low concentration, for example, when compared with the antisense method, and is expected as a potent method for treating diseases caused by various viruses and genetic diseases, which have previously been considered to be difficult to cure.
A naturally occurring DNA oligomer or RNA oligomer, when used in the antisense method or the RNAi method described above, is very unstable biologically, because the oligomer undergoes rapid hydrolysis by various nucleases in blood. In order to solve such a problem, a modified nucleic acid in which a phosphate binding site in the nucleic acid is converted to a methyl phosphorate bond, a modified nucleic acid in which a phosphate binding site is converted to a phosphorothioate bond, or the like is well known.
Also, it has been reported that as an open circular modified nucleic acid having a carbon-carbon bond cleaved at the 2′- and 3′-positions, an UNA (unlocked nucleic acid: 2′,3′-seco-RNA) monomer represented by the following formula:
wherein B represents a nucleobasecan be introduced to siRNA to thereby enhance the stability of the siRNA in blood, increase its degrading activity against a target gene, and suppress an off-targeting effect (Non Patent Literature 2). Alternatively, Patent Literature 1 has proposed the Introduction of an UNA monomer represented by the following formula:
wherein Z represents H, OH, CH2OH, CH3, or a C2-22 alkyl strand into siRNA.